COVID-19 and therapeutic drug discovery possibilities for IonFlux

SARS-CoV-2, the virus responsible for the recent global pandemic and the disease known as COVID-19, is part of a viral family which includes SARS-CoV-1 and MERS-CoV ^{[1], [2]}. This positive-stranded RNA virus shares many structural similarities with other SARS viruses, including several capsule proteins of interest, S (spike) protein and E (envelope) protein ^[2]–[5]. S-protein facilitates the viral entry into the host and hence is a prime target for vaccine research ^[4]. The E-protein on the other hand is a “viroporin” and hence functions as an “ion channel”. When isolated and transfected into mammalian cells, ionic currents passing through the cation selective E-protein can be recorded and compared to wild type non transfected cells ^{[3], [6]–[8]}.

Research on SARS-CoV-1 E-Protein has demonstrated that it’s activity is behind the “cytokine storm” in the lungs of those infected with the coronavirus, leading to edema and respiratory problems ^{[4], [5], [9]}. In fact, the malfunction of this protein has been linked to a decrease in pathogenesis ^[2], and blocking its activity lead to higher survivability of animal hosts. Recent papers looking at the sequenced SARS-Cov-2 E-protein demonstrated high conservation to the E-protein from SARS-Cov-1 ^{[2], [4]} giving credence to the hypothesis that similar modulation of the SARS-Cov-2 E-protein may deliver therapeutic benefits and improve patient outcomes. In fact, known viroporin blockers like Amantadine are being presented already as therapeutic agents for Covid-19^[10], leading the way for more ion channel blockers to be re-assessed as viroporin modulators.

Fluxion’s automated patch clamp system, IonFlux, is used globally for high throughput development and profiling of ion channel-modulating drugs. The IonFlux system may offer an ideal solution for testing potential compounds against the SARS-CoV-2 viroporin. Testing of existing approved and investigational drugs with established safety profiles may lead to shortened timelines that can accelerate introduction of potentially life-saving drugs.

References:

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[9] J. Torres, W. Surya, Y. Li, and D. Liu, “Protein-Protein Interactions of Viroporins in Coronaviruses and Paramyxoviruses: New Targets for Antivirals?,” Viruses, vol. 7, no. 6, pp. 2858–2883, 2015, doi: 10.3390/v7062750.
[10] G. E. A. Abreu, M. E. H. Aguilar, D. H. Covarrubias, and F. R. Durán, “Amantadine as a drug to mitigate the effects of COVID-19,” Med Hypotheses, vol. 140, p. 109755, 2020, doi: 10.1016/j.mehy.2020.109755.

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